Apparatus for measuring prothrombin time



Oct. 8, 1963 M. L. BARNES 3,106,090

APPARATUS FOR MEASURING PROTHROMBIN TIME Filed May 51, 1960 3 Sheets-Sheet 1 TOP WALL LEFT SECTION 5 COVER Q v TOP WALL Q J 57 4a [RIGHT END WALL :s POCKET 5a. K E I 2 1 ---TRAY 30 FRONT $105 4 WALL 2 FIG. I

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\ Momk BOX l L\ i-TRAY 3o 8 IIII W3 THERMAL CHAMBER 7 INVENTOR MALCOLM L. BARNES ATTORNEY Oct. 8, 1963 M. L. BARNES 3,106,090

APPARATUS FOR MEASURING PROTHROMBIN TIME I Filed May 51, 1960 3 Sheets-Sheet 2 GLASSSZx if 5l f 50 J -50 A: N I I5 I 1\ l4 5 l4 AN 37 27 B 040 38 Hs'aim I STEM4I l6 1 Box|- I\ MOTOR g FAME q RE INVENTOR MALCOLM L. BARNES BY MM ATTORNEY Oct. 8, 1963 M. L. BARNES APPARATUS FOR MEASURING PROTHROMBIN TIME Filed May 31, 1960 BAND 4O STEM 4| 3 Sheets-Sheet 5 SLIDE 27 38 SLIDE HOLDER 39 commou AXIS 44 IN VEN TOR. MALCOLM L. BARN ES BY MW ATTORNEY United States Patent ()fiice Edhhfihfi Patented Oct. 8, 1963 3,1tl5,0% APPARATUS FGR MEASURING PRQTIHZOMBW TlME Malcolm L. Barnes, Lonisviile, Ky., assignor to Norton Infirmary Institute of Research, Louisville, Ky, a corporation of Kentucky Filed May 31, 196%, er. No. 32,622 6 Claims. (Cl. 73-53) A heart attack or myocardial infarction results when the blood supply to any part of a heart muscle is interrupted. For example, if one of the coronary arteries becomes obstructed, then that portion of the heart supplied by that artery is damaged. The major source of obstructions is blood clots. Recent developments indicate that once clotting has started, it is prone to continue. One way of preventing continuing damage to the heart muscle is to slow down the bloods tendency to clot and this can be readily done with anti-coagulant drugs. But extreme care must be exercised because the response of different patients to these drugs differs and, if one patients response is too high, he may hemorrhage. To maintain the drum dosage for a given patient at a proper level, it is necessary to make prothrombin or blood clotting time determinations at first daily; later, once or twice a week; and finally, once a month as conditions dictate.

At the present time, the Quick method is the most reliable and widely used method of making a prothrombin determination. it usually requires a patient to have accessible veins for puncture and to be in the hospital so that the test can be carried out under standard conditions in the laboratory where the necessary equipment is available.

A second capillary method which is less commonly used, comprises: (1) cleaning the tip of a finger of the patient with 70% alcohol; (2) making a two millimeter deep puncture in the finger tip with a lancet; (3) drawing 20 cubic millimeters of whole blood from the finger into a pipette; (4) blowing that blood forcibly into the well of a deep well slide already containing an equal amount of thromboplastin and immediately stirring the contents of the well momentarily with the pipette to form a somewhat homogeneous mixture; (5) manually manipulating the slide in a manner effective to flow the mixture along the'sloping walls of the well in a direction (and at a slow speed) such as to rotate it slowly about the vertical center thereof; (6) determining, by observation, when the mixture has coagulated to a desired degree, which establishes the end of the coagulating time period; and 7) measuring the elapsed time between the beginning of the stirring operation and end of said coagulating time period. While this second method offers certain advantages, it is difficul-t to control, requiring a high degree of skill to give results which are both accurate and reproducible. For example, different operators will normally obtain difierent results under similar operating conditions.

The principal object of the present invention is to retain the advantages and overcome the disadvantages of the foregoing second capillary method.

Another important object is to provide a means for practicing the second method which renders it easy to control and capable of giving accurate results when operated by the same operator or by different operators.

,A further object is to provide, for use in practicing the second method, an apparatus which may be simply and inexpensively manufactured and easily and quickly operated, under automatically controlled conditions, in a hospital, home, automobile or other place where alternating or battery current is standardly available to give consistently reproducible and highly reliable results in a relatively short period of time.

This invention resides in the discovery that accurate resuits, (i.e. consistently reproducible and highly reliable results) may be quickly obtained in practicing the second capillary method when the requisite accessories (i.e. the thromboplastin, pipette and slide) are all preheated to a desired temperature, preferably approximating body temperature, and the preheated slide, with its charge of preheated thromboplastin and of blood, is supported in a similarly preheated atmosphere and moved at a predetermined slow speed and in a manner eifective, to cause the charge on the slide to move slowly along the slide. .By supporting the slide so that its charge is readily visible, an observer or operator can readily see when the charge has coagulated to the desired degree and therefore accurately measure the coagulating or prothrombin time.

All of the requisite apparatus can be housed in a thermal box of a size which is easy to carry. In a hospital, home or any other place where 60 cycle A.C. current is readily available, it is a simple matter to maintain the atmosphere within the box at a predetermined temperature since this requires nothing more than a fan for circulating air within the box, an electric heater for heating that air and a thermostat for controlling the operation of the heater. The same is true where battery current is available. With a portable battery, the box may be maintained in its preheated condition as it is carried from one AC. outlet to another, as, for example, from hospital to home.

The invention is illustrated in the accompanying draiwing wherein:

FIG. 1 is a top plan view of a thermo box constructed to carry out the invention;

FIG. 2 is a partly broken vertical sectional view taken along the longitudinally extending line 2-2 of MG. 1;

FIG. 3 is a vertical sectional view taken along the transversely extending line 33 of FIG. 1;

*FIG. 4 is a vertical section taken along the transverse- 1y extending line 44 of FIG. 1; and

FIG. 5 is an enlarged elevational view partly in section of the mechanism for supporting and rotating a charge of preheated thromboplastin and of blood.

The illustrated apparatus comprises: (a) a thermal box having a thermal chamber; (b) thermostatically controlled heating means for maintaining said thermal chamber at a predetermined temperature; (0) accessory means including thromboplastin, a pipette and a slide; (d) means for preheating accessory means to a predetermined temperature; (e) motorized supporting means for supporting and moving said slide within said thermal chamber at a predetermined speed and in a manner efiective, when a charge of intermixed thromboplastin and blood is provided on said slide, to cause said charge to move slowly along the slide; (1) means rendering the charge on said slide readily visible so that an operator may, by observation, determine when such charge has initially reached that degree of coagulation which establishes the end of the coagulating time period; and (g) manually controlled timing means for measuring thecoagulating time period.

THERMAL BOX The thermal box 1 may be composed of any suitable material and fashioned in any suitable shape, As illustrated, it comprises: front and rear side walls, the front wall being designated by the numeral 2; left and right end walls, the right end wall being designated by the numeral 3; top and bottom walls, the top wall having a right section 4 and a left section 5; and a cover 6 hinged to the upper edge of the rear side wall. All walls may be composed of a heat insulating material such as wood and all walls preferably are composed of wood except the right end wall 3 and the right section 4 of the top wall, both of which are preferably composed of trans- TI-IERMOSTATICALLY CONTROLLED HEATING MEANS The thermostatically controlled heating means preferably includes: means for circulating a stream of air within said thermal chamber; means for heating said air; and means for thermostatically controlling the operation of said heating means.

Air Circulating Means The air circulating means includes: an electric motor '11 in the motor chamber on the left side of partition 8; and a fan 12 in the thermal chamber 7 on the right side of partition 8, the fan being mounted on a projecting end of the motor shaft. To give the air movement created by the fan a definite pattern of flow and thereby promote uniform temperature, the thermal chamber 7 is divided by a vertically arranged transverse partition 13 into left and right sections while the right section thereof is subdivided by a horizontally arranged transverse partition 14 into a vertically deep air receiving passageway extending horizontally along the bottom wall from the partition 13 to the right end wall 3 and a vertically shallow return passageway extending horizontally along top wall 4 from the right end wall 3 back to the vertical partition 13, these passageways being vertically con nected together along the right end wall 3. With this arrangement, the fan 12 is positioned within a large lower opening in partition 13 to blow air into the lower air receiving passageway while the partition 13 is provided with a series of small openings 15 to return air from the air return passageway into the left section of the thermal chamber on the suction side of the fan 12.

Before passing it may be noted that the horizontally arranged partition 14 may be supported on the side walls of the box but, to facilitate assembly, it is preferably composed of sheet metal and supported on sheet metal side walls 16.

Air Heating Means The air heating means includes: one electric heater mounted in the thermal chamber for use with alternating current; a second electric heater mounted in the thermal chamber for use with direct current; and means selectively operable at the will of the operator for rendering a selected one of said heaters operable under the control of said thermostatic means.

The alternating current heater comprises a suitable resistance heater 18 located on the suction side of the fan and mounted on transverse partition 13. The direct current heater comprises a suitable resistance heater 19 also located on the suction side of the fan and mounted on transverse partition 8.

To render these heaters selectively operable at the will of the operator, a pair of switches is mounted on the left section of the top wall, one switch 20- controlling the connection of the A.C. heater 18 to commercial 60 cycle A.C. current and the other switch 21 controlling the connection of the DC. heater 19 to a suitable source of DC. current such as a battery. To prevent the accidental operation of the battery switch 21, it is covered by a metal saddle bridge 22 which must be removed before switch 21 can be operated.

Thermostatic Control Any conventional thermally responsive control means may be used to sense the prevailing temperature in the thermal chamber 7 and turn the operating heater on and i off to maintain that temperature. In the construction illustrated, a thermostat 24 is mounted to project from the top wall 4 downwardly into the return air passage of chamber 7. It will be understood, of course, that this thermostat operates conventionally to open the heater circuit either directly or indirectly through some interposed mechanism (not shown) such as a relay.

ACCESSORY MEANS The accessory means, requisite for the practice of the second capillary method, comprises: a supply vessel 26 of thromboplastin; one or more deep well slides 27; and one or more pipettes 28 for transferring thromboplastin and blood to the slide.

ACCESSORY PREHEATING MEANS The various accessories should be preheated to and maintained at the desired temperature. To this end, they may be stored on or in said thermal box in a position exposing them to the heat within said thermal chamber sufliciently to maintain them at said predetermined temperature. In the structure illustrated, this is accomplished by mounting the thromboplastin vessel 26 so that it projects into the thermal chamber 7, by mounting and by storing the slides 27 and pipettes 28 bodily Within the thermal chamber 7.

Accordingly, the top wall 4 is provided with a suitable opening into which a holder 29 is mounted, this holder projecting downwardly into the thermal chamber 7. The holder 29 is designed to receive the thromboplastin vessel 25 while the latter is designed to close the opening in which the holder is mounted. With this arrangement, the thromboplastin vessel is constantly subject to the temperature of the air in the return air passage and is thus maintained at the predetermined temperature of the thermal chamber atmosphere which, as stated previously, preferably approximates body temperature.

The top wall 4 of the thermal box is also provided with another opening to receive a downwardly depending tray 30 within and on which a stack of slides 37 may be stored. The tray 30 normally closes the top opening through which it projects and is provided on its projecting end with a handle 31 to facilitate its removal and replacement.

The pipettes 28 may also be stored in a tnay 32, which is wholly contained within the thermal chamber 7, and rendered accessible by slid-ing the right end wall 3 upwardly to an extent permitting an operator to reach into the tray 32 and remove or replace a pipette. If desired, however, the pipette tray 32 may be slidably mounted in a side, end or top wall opening for operation in a manner similar to that of the deep well slide tray 30.

MOTORIZED SLIDE SUPPORTING AND MOVING MEANS The motorized supporting means functions first to support a slide within the thermal chamber and second to move it at a predetermined speed and in a manner effective, when a charge of said mixture is placed on the slide, to cause said charge to move slowly along the slide. While the motorized means may be designed to move the charge in any suitable way, preferably rotationally, the mechanism shown effects a rotary movement of the change by combining endwise rocking movement of the slide with side-wise rocking movement thereof.

The illustrated embodiment of this mechanism comprises: (a) an assembly located within chamber 7 and including (1) a fixed horizontal axis, a rocking horizontal axis and a vertical axis all passing through a common center area at right angles to each other, (2) a swinging bracket mounted on the box for swinging movement parallel to and about the fixed horizontal axis and (3) a slide holder mounted on the swinging bracket first to rock transversely to and about the fixed horizontal axis as the bracket swings parallel thereto and second to swing relative to the bracket in a direction extending parallel to and about the horizontal rocking axis; (1)) means for tilting the assembly about its center point area so that its vertical axis declines from that center point area away from the vertical gravitational axis of that area; and (c) means for swinging the tilted assembly around said vertical gravitational axis in a manner causing'its tilted axis to describe a cone around said gravitational axis.

Assembly-Axes, Swinging Bracket and Slide Holder The assembly has a fixed horizontal axis 34, a horizontal rocking axis 35 and a vertical axis. 36, all extending at right angles to each other and all intersecting at, or ad jacent to, a center point or area.

The swinging bracket comprises: a horizontally wide, vertically-shallow strap-like U-shaped first member 37; and an identical strap-like U-shaped second member 38 horizontally arranged at right angles thereto. The ho zontal bights of these two members are centered about the vertical axis 36 of the assembly and rigidly secured together. The first bracket member 37 is located in an opening of the horizontal partition 14. By means of suitable tnunnions at the upper ends of its legs, it is pivotally connected to that partition 14 for swinging movement parallel to and about the fixed horizontal axis 34. As this bracket swings back and forth about axis 34, it rocks the slide bolder endwise about axis 34.

The slide holder 39 is in the form of a shallow pan dimensioned to receive a deep well slide and removably support it while holding it against relative sliding movement. The slide holder or pan 39 is bodily carried by the supporting bnacket 37-38 as a whole to rock endwise transversely to and about the fixed horizontal [axis 34 as the bracket swings about that axis. It is also pivotally connected to the upper ends of the legs of bracket member 33 [for relative sidewise swinging movement parallel to and about the horizontal hocking axis 35. This pivotal connection is supplied by an axle, which is also designated by the numeral 35, since it coincides with the horizontal rocking axis 35.

The slide holder or pan 33 has an arcuate strap band 40 extending from adjacent one of its ends to the other on its back or lower side. This band 40 carries a stem 41 which is located in and extends along the vertical axis 36 of the assembly. The stem 41 may be moved back and forth parallel to axis 34 and tnansversely to axis 35 so as to swing the slide holder sidewise. It may also be moved reversely to rock the slide holder endwise. By tilting the stern and then moving it around the gravitational axis of the common center point area, the slide holder can be moved in a fashion combining its rocking and swinging movements.

Assembly Tilting Means The assembly tilting means comprises: a shaft 43 having a common axis 44 with the gravitational axis of the center point area of the assembly; and a crank arm 45 mounted on the shaft 43 to extend outwardly therefrom with its outer end connected to the stem 41 tor the purpose of holding the assembly and its vertical axis 36 in a tilted position. In this tilted position, the vertical axis 36 of the assembly declines from the center point area of the assembly outwardly away from the common axis 44- of the center point area and shaft 43.

Assembly Moving Mean The assembly moving means comprises an electric mot-or 47 controlled by switch 48. The motor 47 is connected to rotate shaft 43 at a speed which should be less than 60 rpm. and which preferably is about 35 rpm. The motor does not rotate the assembly about its tilted axis 36 but it does move the point of connection, between the arm 45 and the stem 41, circularly about the common axis 44, thereby swinging the assembly bodily about that axis in a manner causing the tilted vertical axis 36 of the assembly to describe a cone aboutthe common axis 44.

With this arrangement the degree and direction or" endwise and sidewise tilt of the slide, in locations beginning with FIG. 4 and proceeding clockwise therefrom at intervals, is indicated in Table I which follows:

TABLE I Tilt of Slide Location of Slide Endwise Sidewise Degree Direction Degree Direction Zero Max- Forwardly. Zcr0 Max- Rearwardly.

MEANS RENDERING CHARGE VISIBLE In order to render the charge on a slide highly visible, as it is supported and moved within the thermal chamber 7, the top wall sect-ion 4 is made of transparent plastic while the box is provided with at least two electric lamps 50, which are housed within suitable reflectors 51. These reflectors are arranged to reflect light obliquely downwardly onto the top of a deep well slide which is being supported on the swinging bracket and appropriately moved. To increase the visibility still further, a magnifying glass 52 is mounted directly over the supported deep well slide. The magnifying glass 52 is supported on a framework 53 which is hinged at one end to the box so that it may be swung aside to uncover an opening 54 providing access to the interior of the thermal box for slide removal, replacement and changing purposes.

OPERATION The illustrated apparatus enables the second capillary method to be practiced under controlled conditions insuring accurate and reproducible results. The thermal chamber 7 should, of course, be maintained at body temperature with the accessory means at the same temperature. With the apparatus thus conditioned for use, the second capillary method may be practiced as follows: (1) remove a preheated deep well slide 27 from the slide holding tray 30; (2) draw 20 cubic millimeters of thromboplastin from the preheated supply vessel 26 with a preheated pipette 28; (3) blow the thromboplastin into the centrally disposed well of the preheated slide 27; (4) place the slide 27 on the swinging support 3738 before or after the thromboplastin blowing openation; (5) start motor 47 through switch 48 to institute the movement of the swinging support 3738 at any time prior to the blood blowing openation; (6) clean and puncture the finger in a conventional way; (7) draw 20 cubic millimeters of whole blood from the finger into a preheated pipette 28; 8) blow that blood forcibly into the rotating throm'boplastin charge on the moving slide 27; (9) immediately stir the blood-thrombopl-astin charge with the pipette to form a somewhat homogeneous mixture; (10) simultaneously start the timer 55 through switch 57 at the beginning of the blood stirring operation; (11) determine by observation through glass 52 when the moving mixture has coagul-ated to a desired degree and then stop the timer; and (12) read the elapsed time, between the beginning of the stirring operation and the end of said coagulating time period, on the timer 55.

When the apparatus is operated in this manner, the results obtained by dilferent operators are either the same or are not significantly diiferent and this is true regardless of which of'the three wells in the slide 27 is used to receive the charge.

For the sake of simplicity and clarity, the term prothrombin time is used herein in a generic sense meaning the coagulating time period of the blood mixture. Similarly, the term thromboplastin is used herein in a generic sense meaning any material which is mixed with the blood to institute the blood coagulating operation, the duration of whichdetermines the prothrombin time.

Having described my invention, I claim:

1. Apparatus for use in measuring the prothrombin time of a liquid mixture of blood and thromboplastin, comprising: a box having a thermal chamber containing a gaseous atmosphere; means for maintaining said thermal chamber atmosphere at a predetermined temperature; accessory means including a slide; motorized supporting means for supporting said slide within and wholly surrounded by the gaseous atmosphere of said thermal chamber and for moving said slide at a predetermined speed and in a manner efiective, when a charge of said mixture is placed on said slide, to cause said charge to move slowly along the slide; and means rendering the charge on said slide readily visible so that an operator may, by observation, determine when such charge has initially reached that degree of coagulation which establishes the end of the coagulating time period.

2. The apparatus of claim 1 wherein: said temperature maintaing means holds said thermal chamber atmosphere at a temperature approximating body temperature.

3. The apparatus of claim 1 wherein said temperature maintaining means includes: means for circulating a stream of air within said thermal chamber; means for heating said air; and means thermostatically controlling the operation of said heating means.

4. The apparatus of claim 1 wherein: said slide has a deep Well to receive said charge; and said slide moving means is effective to rotate a charge in said deep well.

5. The apparatus of claim 4 wherein: said moving means moves said slide in a manner combining end-to-end rocking with side-to-side rocking movements.

6. Apparatus for making prothrombin time determinations on blood samples comprising a normally closed test chamber,

means for maintaining a substantially constant selected temperature within said chamber,

a movable support within said chamber for supporting in Wholly enclosed relation within the test chamber a test container adapted to receive preselected proportions of blood samples and clotting reagents,

universal mounting means for said movable support permitting tilting of the support and associated test container in a circular path about a selected vertical axis,

means for mechanically imparting uniform cyclic movement to the support and associated test container to effect cyclic tilting movement of the same in a manner to induce continuous swirling motion of the blood sample,

means permitting visual observation from externally of the chamber of the admixed blood sample and reagent in the test container carried by said support, and

means for timing the interval between the admixture of the blood sample and the reagent and the clotting of the blood sample.

References Cited in the file of this patent UNITED STATES PATENTS 2,225,566 Ide Dec. 17, 1940 2,277,605 Palitzsch Mar. 24, 1942 2,478,785 Shapiro Aug. 9, 1949 2,584,435 Doerr Feb. 5, 1952 2,755,173 Shore July 17, 1956 2,878,715 Rhees Mar. 24, 1959' 2,963,898 Reynolds et al. Dec. 13, 1960 2,967,424 Hoover Jan. 10, 1961 3,020,748 Marshall Feb. 13, 1962 FOREIGN PATENTS 961,221 Germany .t Apr. 4, 1957 

1. APPARATUS FOR USE IN MEASURING THE PROTHROMBIN TIME OF A LIQUID MIXTURE OF VLOOD AND THROMBOPLASTIN, COMPRISING: A BOX HAVING A THERMAL CHAMBER CONTAINING A GASEOUS ATMOSPHERE; MEANS FOR MAINTAINING SAID THERMAL CHAMBER ATMOSPHERE AT A PREDETERMINED TEMPERATURE; ACCESSORY MEANS INCLUDING A SLIDE; MOTORIZED SUPPORTING MEANS FOR SUPPORTING SAID SLIDE WITHIN AND WHOLLY SURROUNDED BY THE GASEOUS ATMOSPHERE OF SAID THERMAL CHAMBER AND FOR MOVING SAID SLIDE AT A PREDETERMINED SPEED AND IN A MANNER EFFECTIVE, WHEN A CHARGE OF SAID MIXTURE IN PLACED ON SAID SLIDE, TO CAUSE SAID CHARGE TO MOVE SLOWLY ALONG THE SLIDE; AND MEANS RENDERING THE CHARGE 